The story of living in spite of melanoma, metastasis, vaccines, anti-PD-1, lung removal, and stereotactic radiation. The story of life with family and friends. {Posts under ~ Sew Chaotically, Travel Chaotically, and Chaotic Cookery also housed within! A girl's gotta have fun!}

About Me

Who am I? That is a question the rest of you could probably answer better than I. I am a wife, mother, daughter, sister, friend, pediatric nurse practitioner, cook, teacher, gardener, lover of words and music, occasional seamstress, and homemaker. I do have a couple of talents of questionable merit: I can create a decent meal in less than 30 minutes. I can feed and/or soothe almost any baby. And I can remember practically any song I've ever heard. For the rest, I'd rather those who know me decide.

Sunday, July 5, 2015

Combo's looking good....but if PD-L1 positive...just do nivo!!??

Melanoma was again a focus of attention at the 2015 American Society of
Clinical Oncology (ASCO) Annual Meeting, in particular the use of
combination treatment strategies involving immunotherapies and/or
targeted agents. New data on targeted therapies confirmed previous
findings, with combined BRAF inhibitor (vemurafenib) plus MEK inhibitor
(cobimetinib) improving progression-free survival (PFS) compared to
vemurafenib monotherapy in patients with BRAFV600 mutation-positive
tumors (CoBRIM trial). Positive results were also seen with combined
dabrafenib and trametinib in patients with BRAF V600E/K metastatic
melanoma and encorafenib plus binimetinib in BRAFV600-mutant cutaneous
melanoma. Even more interesting news centered on the use of combination
immunotherapy, in particular the randomized, double-blind CheckMate 067
study in which median PFS with nivolumab plus ipilimumab was
11.5 months, compared to 2.9 months with ipilimumab alone and
6.9 months with nivolumab alone. Of interest, in patients with
≥5% PD-L1 expression, median PFS was 14 months with the combination or
with nivolumab alone compared with 3.9 months in the ipilimumab group,
while in the PD-L1 negative cohort, the combination remained superior to
both monotherapies. Given that combination therapy was accompanied by a
high occurrence of side-effects, this raises the suggestion that
combination therapy might be reserved for PD-L1 negative patients only,
with PD-L1 positive patients achieving the same benefit from nivolumab
monotherapy. However, overall survival data are awaited and the
equivalence of single agent to the combination remains unconvincing.
Interesting data were also reported on the combination of T-VEC
(talimogene laherparepvec) with ipilimumab, and the anti-PD-1 agent
MEDI4736 (durvolumab) combined with dabrafenib plus trametinib. Emerging
data also suggested that predictive markers based on immunoprofiling
and mismatch repair deficiency may be of clinical use. In conclusion,
the use of combination approaches to treat patients with melanoma, as
well as other cancers, is no longer a just a wish for the future but is
today a clinical reality with a rapidly growing evidence-base. Moreover,
the most exciting consideration is that this is far from the end of the
story, but rather a fantastic introduction.

Thoughts:1. What I've been saying....COMBO's!!!!2. But, which one???3. If you are BRAFV600 positive and are ready for BRAFi...these combo's are doing very well: vemurafenib with combimetinib, dabrafenib with trametinib, and encorafenib plus binimetinib.4. Combo immunotherapy: CheckMate 067 showed us PFS of 11.5 months on the ipi/nivo combo vs 2.9 months on ipi alone and 6.9 months on nivo alone. BUT!!!!! In PD-L1 positive patients PFS was 14 months on just nivo vs 3.9 months for ipi. In PD-L1 negative patients the ipi/nivo combo was better than either monotherapy. SO! Since the ipi/nivo combo has more side effects but gives you no better results if you are PD-L1 positive....it probably makes more sense to just do nivo alone!5. T-VEC with ipi and yet another anti-PD1 product (MEDI4736/durvolumab) with dabrafenib plus trametinib seem promising as well.6. Here's hoping that markers and combo's become more clarified and APPROVED very soon.7. Thanks, ratties!!!
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